Anti-GDF15 antibodies and drug regimens for cancer treatment

Abstract

The present invention relates to anti-GDF15 antibodies and dosing regimens for the treatment of cancer in human patients using anti-GDF15 antibodies. The inventors have identified the mechanism by which GDF-15 blocks the adhesion and entry of primarily T lymphocytes into tissues. Therefore, the present invention has established a novel treatment approach in which blocking GDF-15 using the antibodies of the present invention promotes the entry of effector T cells into tumor tissues, thereby enabling the treatment of cancer in human patients.

Claims

1. A composition for use in a method for treating cancer and / or cancer cachexia in a human patient, comprising an anti-GDF-15 antibody, wherein the heavy chain of the antibody comprises the amino acid sequence represented by SEQ ID NO: 8, and the light chain of the antibody comprises the amino acid sequence represented by SEQ ID NO:

9.

2. The aforementioned anti-GDF-15 antibody is (i) to (iii) below: (i) A drug regimen of doses of 0.3, 1.0, 3.0, 10.0 or 20.0 mg / kg and of at least one administration cycle, wherein the administration cycle is for a period of 2 weeks, and the dose is administered at least once in each of the at least one administration cycles. (ii) A drug regimen of a dose of 10-20 mg / kg and of at least one administration cycle, wherein the administration cycle is for a period of 4 weeks, and the dose is administered at least once in each of the at least one administration cycle, or (iii) A drug regimen of a dose of 10-20 mg / kg and at least one administration cycle, wherein the administration cycle is for a period of 3 weeks, and the dose is administered at least once in each of the at least one administration cycle. The composition according to claim 1, administered according to one of the following.

3. The composition according to claim 1 or 2, wherein the anti-GDF-15 antibody can be obtained by expression in CHO cells.

4. The composition according to claim 2, wherein the concentration of GDF-15 in the patient's serum / plasma is less than 10 ng / mL at the end of the administration cycle.

5. The composition according to claim 2, wherein the administration cycle is for a period of 3 weeks, and the dose is administered at least once in each of the at least one administration cycle.

6. The composition according to claim 2, wherein the administration cycle is for a period of 4 weeks, and the dose is administered at least once in each of the at least one administration cycles.

7. The composition according to claim 2, wherein the drug regimen comprises a plurality of administration cycles.

8. The composition according to any one of claims 1 to 7, wherein the anti-GDF-15 antibody is administered in combination with a checkpoint inhibitor, and the checkpoint inhibitor is selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, or an anti-CD40 antibody.

9. The composition according to claim 2, wherein the anti-GDF-15 antibody is administered in combination with a checkpoint inhibitor, and the checkpoint inhibitor is administered in the same drug regimen as the GDF-15 antibody, or the checkpoint inhibitor is administered prior to the administration of the GDF-15 antibody.

10. The composition according to any one of claims 1 to 9, wherein the cancer is selected from the group consisting of brain cancer including glioma, nervous system cancer, melanoma, lung cancer, head and neck cancer, urothelial carcinoma, liver cancer, endometrial cancer, cervical cancer, gastric cancer, renal cell carcinoma, Ewing's sarcoma, non-small cell lung cancer and small cell lung cancer, lip cancer, liver cancer, leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, bladder cancer, cervical cancer, endometrial cancer, testicular cancer, thyroid cancer, kidney cancer, gallbladder cancer, multiple myeloma, nasopharyngeal cancer, laryngeal cancer, pharyngeal cancer, esophageal cancer, gastric cancer and colorectal cancer, pancreatic cancer, prostate cancer, ovarian cancer, breast cancer, and carcinoma of unknown primary origin.

11. The composition according to claim 2, wherein the dose of the anti-GDF-15 antibody is administered intravenously.

12. An anti-GDF-15 antibody, wherein the heavy chain of the antibody contains the amino acid sequence represented by SEQ ID NO: 8, and the light chain of the antibody contains the amino acid sequence represented by SEQ ID NO:

9.

13. The antibody according to claim 12, which can be obtained by expression in CHO cells.

14. A formulation comprising an anti-GDF-15 antibody, wherein the formulation comprises 10 to 50 mg / ml of the anti-GDF-15 antibody, the heavy chain of the antibody comprises the amino acid sequence represented by SEQ ID NO: 8, and the light chain of the antibody comprises the amino acid sequence represented by SEQ ID NO:

9.

15. The formulation according to claim 14, comprising histidine / histidineHCl, sucrose, arginine-HCl, and polysorbate at a pH of 5 to 6.

16. The formulation according to claim 14 or 15, comprising 25 mg / ml of the GDF-15 antibody, 20 mM histidine / histidine HCl, 150 mM sucrose, 50 mM arginine-HCl, and 0.02% w / v polysorbate 20 at pH 5.5.

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